Request for Proposals: Targeted Biomedical Research
Exploring the mechanisms for HIV persistence and the potential for HIV eradication
Deadline: Closed

Available Support

amfAR, The Foundation for AIDS Research, is pleased to announce the availability of targeted support for biomedical research projects relevant to exploring the mechanisms for HIV persistence and the potential for HIV eradication.

Funding will be available for:

Research Grants— $208,333 for direct costs plus up to 20 percent for indirect costs ($250,000 maximum total costs). The performance period for grants awarded under this RFP will be for two years starting February 1, 2012.

Background and Areas of Interest

amfAR's research program is driven by the Foundation's mission to end the global AIDS epidemic through innovative research. amfAR plays a uniquely important role in AIDS research, identifying critical gaps in our knowledge of HIV and AIDS, and supporting groundbreaking studies that often lack the preliminary data required by more traditional funders. The Foundation's research program focuses on efforts to prevent HIV infection among vulnerable populations and to improve treatment, with the ultimate goal of eradicating the virus in people living with HIV infection.

This RFP solicits proposals relevant to exploring the mechanisms for HIV persistence and the potential for HIV eradication. Highly active antiretroviral therapy (HAART) has significantly impacted the health of individuals infected with HIV-1. However, if therapy is interrupted, there is a rapid resumption of viral replication. Understanding the mechanisms by which the virus is able to persist in the face of therapy is necessary in order to identify strategies that may interrupt viral persistence and ultimately lead to viral eradication. amfAR wishes to support basic, clinical, and especially translational research exploring the mechanisms whereby HIV infection persists; the chronic nature of viral reservoirs and latency; and barriers to the eradication of HIV, with the potential goal of ultimately eliminating HIV infection.

Understanding and characterizing cellular and tissue locations of reservoirs and their relative importance in maintaining infection in the face of ART and the immune system

Understanding the extent to which persistence is due to true latency versus low level replication. How does the effect of ART differ in each case?

Is there a threshold viral load below which infection will not be re-seeded?

Studies in elite controllers and/or acute (i.e. the absence of antibody positivity) infection cohorts that may help define new mechanisms of persistence that are not HLA-driven.

Does persistent immune activation point to a need for long-term immune reconstitution strategies? Are there benefits to immune therapy?

Improved assays to quantify integrated versus unintegrated DNA, or characterize replication competence. Do these differ between tissues, in patients treated during acute versus chronic infection, or in progressors versus controllers?

Improved assays to more efficiently and inexpensively measure extremely low viral load (e.g., to 0.01 copies/ml) or (changes in) the size of the persistent reservoir.

Deep sequencing approaches to compare viruses in different tissue compartments with those in plasma following treatment interruption, with a view to identifying sources of viral rebound

What are the consequences of chronic immune activation, in the presence or absence of ART, on tissues such as the gut, and can the damage be reversed if immune activation is controlled?

Definitions and exclusions:

Basic researchApplicants are encouraged to submit proposals using appropriate in vitro or ex-vivo techniques. Attempts to validate existing in vitro or ex vivo models, and to develop new models, including animal systems, are also encouraged.

Clinical researchApplicants who wish to use amfAR funding to conduct a discrete clinical research project, for example as a definable, distinct part of an ongoing clinical trial, should clearly describe how amfAR funding can support the entire discrete project for which funding is sought. Proposals for which amfAR funding will represent a small fraction of pooled resources (i.e., to "top up" total funding of a clinical research project) will not be considered.

Translational researchApplicants are especially encouraged to design research studies in which the findings from basic science can be quickly and efficiently applied to medical practice. Such applications are likely to include multi-disciplinary collaboration and a description of the ways in which basic science findings generated with this funding can or will be tested (using this funding) in an appropriate non-human primate model or in patients.

CollaborationProposals may include component projects (i.e., two or more distinct but interrelated projects, each under the lead of different investigators at the same or other institutions). Please see the Qualifications section for additional information.

Special notes

Please note that this RFP differs from recent ones in the following ways:
• The direct cost maximum is $208,333; total cost maximum is $250,000
• Research grant funding is for a two-year period beginning February 1, 2012
• Proposals for both individual and collaborative research projects are solicited
• It is not required that principal or collaborating investigators hold a faculty-level position

Qualifications

Principal investigators must hold a doctoral level degree and be affiliated with the applicant institution. If a proposal includes subcomponent projects, the principal investigator will be expected to lead one of the component projects, coordinate the development, implementation, and analysis of the project as a whole, and be responsible for the preparation and submission of required progress reports.

Collaborating investigators lead a component project and play an active role in the development, implementation, and analysis of the project as a whole. Collaborating investigators must hold a doctoral degree and may be affiliated with any research organization, including governmental units or agencies.

Please note that all applications will be considered together (i.e., proposals from non-faculty-level researchers will be in competition with proposals from faculty-level investigators).

Types of Funding

Research Grants—Research grants are given to nonprofit institutions worldwide to support investigator-led projects approved by the Foundation. In general, funds are applied to direct costs of salaries and fringe benefits for professional and technical personnel, laboratory supplies and equipment, travel, and the publication of findings. This initiative will provide support for two years without assurance of continued funding.

Research Plan (submitted as a separate document): no more than 1,500 words (single spaced, one-inch margins, Times New Roman 12 point font) including background and rationale, preliminary studies, specific aims, experimental design, procedures, and data analysis to be used.

Please obtain the LOI INSTRUCTIONS for detailed directions.

Important NoticeElectronic (e-mailed) LOIs that are received late, are incomplete, or exceed word count limitations will not be accepted for review. Fax submissions are not accepted. Deadline extensions are not available

Submission of an LOI is not a guarantee of eligibility to submit a full application. The pre-application process is highly competitive. Only a limited number of investigators submitting an LOI will be invited to submit a full application.

Policies and Conditions

To Whom Grants Are MadeGrants are awarded to nonprofit institutions; they are not awarded to individual investigators. Accordingly, an application, if solicited, must bear the signature of an official authorized to sign for the institution and, if requested, the applicant institution must submit proof of its nonprofit status. Applications are neither requested nor accepted from for-profit entities. Institution endorsement is not required for Letters of Intent.

By accepting an amfAR grant, the recipient institution will accept full responsibility for the conduct of the investigation and for the acts of the investigator(s). Both are under the direction of the institution and are subject to its medical and scientific policies. Similarly, project personnel compensated in full or in part with funds awarded by the Foundation are employees of the recipient institution; they are not amfAR employees.

Applicants need not be U.S. citizens, and there are no restrictions as to age, color, creed, gender, medical condition, handicap, national origin, parental status, political affiliation, race, religion, marital status, or sexual orientation.

Members of the Foundation’s board of trustees are not eligible as investigators in Foundation-supported research. Members of the Scientific Advisory Committee (SAC) are eligible. Members of the board of trustees and SAC must comply with the Foundation’s policies regarding the avoidance of conflicts of interest.

Allowed Use of Funds

In general, a research grant is applied to direct costs of salaries for professional and technical personnel, laboratory supplies and equipment, travel, and the publication of findings.

Funds are not awarded for the following:

Major construction or the remodeling of facilities (minor alterations are allowed with adequate justification);

The direct cost of support services normally available at a sponsoring institution (e.g., telephone, office furniture, and supplies) except when directly allocable and essential to carrying out the proposed research;

The purchase, lease, rental, or servicing of office equipment;

Funding for dissertation research;

Indirect costs in excess of 20 percent

Indirect Costs—Foundation grants are not meant to cover the total cost of a proposed research project. A grantee institution is expected to provide the necessary physical facilities and administrative services, as well as other supporting services normally available at a sponsoring institution. Expenses generally considered to be indirect costs may be budgeted as direct costs only when required for the operation of remote sites deemed necessary and leased or rented exclusively for conduct of the funded research. Such requests will be carefully assessed for appropriateness and are subject to peer review and administrative approval.

For this RFP, indirect costs are allowed at a maximum rate of 20% of direct costs excluding sub-contracts or sub-awards for component projects. However, indirect costs of up to 20% may be included in payments to sub-recipients.

When an application for project support is submitted to amfAR and also to other grant making agencies, accepted support from the Foundation and from another agency cannot be in duplication.

Recipient institutions agree not to promote or engage in violence, terrorism, or the destruction of any state, and to take prudent measures to insure that they do not provide support through sub-grants or other financing to any entity that engages in those activities.

Restrictions on the Use of Funds Awarded to Foreign OrganizationsUnless written authority is obtained in advance from amfAR, funds from grants awarded to organizations outside of the United States (U.S.) may not be used to support (a) services performed in the U.S., or (b) travel to or from the U.S. Authorization to use funds for such purposes may be obtained by providing either of the following sets of documentation: (1) a copy of U.S. Internal Revenue Service (IRS) form W-8EXP bearing a valid International Taxpayer Identification Number or Employer Identification Number and either (a) an IRS determination letter or (b) written opinion of U.S. counsel that the organization is described in IRS Code section 501(c)(3); (2) alternatively, an applicant organization in a country that benefits from an exemption under a tax treaty with the U.S. should provide (a) a completed copy of IRS form W-8BEN and (b) an affidavit stating the treaty provision under which benefits are claimed and asserting facts pertinent to the treaty provision (e.g., facts to establish that the organization would qualify under IRS code section 501(c)(3)).

Although these documents are not required for LOIs, applicants should anticipate and prepare for their submission as part of the application or award process.

Source of FundsFunds available to the Foundation are obtained principally from private donations.

Review and Approval ProcessamfAR intends to encourage and support HIV/AIDS research of the highest quality. Therefore, every properly prepared and submitted LOI or application received in response to an amfAR solicitation is peer-reviewed by members of the Foundation’s Scientific Advisory Committee (SAC). Each is subject to an overall conformance review by the Foundation staff. Those found to be inconsistent with the guidelines and instructions are eliminated at that time, and the investigator and the applicant institution’s grants official are notified. Applications are solicited from investigators whose letters of intent have been recommended by the Foundation’s SAC. Unsolicited applications are not accepted for consideration.
The SAC, a volunteer body of scientists who are experts in various fields of HIV/AIDS research, evaluates (1) the scientific merit of LOIs and applications; (2) the relevance of the research to the control of the epidemic or to the benefit of patients with AIDS or HIV/AIDS-related conditions; (3) the qualifications, experience, and productivity of the investigator/sponsor; (4) the facilities available; and (5) the likelihood of success. The SAC’s determinations are considered by the amfAR board of trustees, which holds the sole authority to approve project funding.
Submission of an LOI does not guarantee invitation to submit a complete application. The LOI process is very competitive and only a limited number of proposals are approved for additional review.
Written critiques are not available for LOIs.

ConfidentialityThroughout the review and award process, the Foundation respects the privacy of the applicant and endeavors to protect from disclosure any confidential or proprietary information contained in a submitted proposal. However, amfAR has in place no mechanisms to maintain or guarantee confidentiality and, as a not-for-profit corporation, lacks the financial resources to (1) institute such mechanisms or (2) accept liability for the disclosure of information. At the same time, the Foundation does not consider information on an application’s project description form (lay-language summary) to be confidential. That information may be made public as a description of the project being funded by amfAR. Submission of an application or LOI is deemed acceptance of these provisions.

Human and Animal Subjects / BiohazardsApplicants are required to submit documentation of institutional approvals for research involving human or animal subjects or the use or production of biohazards. Research activity may not begin, nor may expenditures be made, until such approvals are received and forwarded to amfAR. Although these approvals are not required at the LOI stage, investigators should prepare to submit them with full applications.